Sensorimotor gating in humans with tinnitus and hyperacusis

描述（由申请人提供）：本研究在耳鸣和耳聋患者中检测感觉运动门控的经典指标——声惊反应（ASR）和脉冲前抑制（PPI）的建议既重要又及时。它的动机是：(i)几乎完全缺乏与人类耳鸣或耳鸣过度相关的ASR或PPI数据，尽管这些措施在客观化和阐明各种其他条件方面取得了成功，这些条件也被认为涉及抑制和过度兴奋的失败，包括精神分裂症，强迫症和图雷特综合征；（ii）动物模型中ASR增强表明耳鸣过度，但缺乏数据验证这一假设；（iii）最近对动物耳鸣间隙检测惊吓反射（GDSR）测试的兴趣激增，该测试尚未在人类中得到验证，并且依赖于ASR和神经回路介导的PPI。拟议的测量人类受试者ASR、PPI和GDSR的实验将测试(1)对耳鸣和耳鸣的机制的见解是否可以从其他研究更深入的神经系统疾病中得到利用，这些疾病的ASR和PPI已经得到了很好的表征；(2)ASR和GDSR测量是否被认为表明动物的耳鸣和耳鸣确实如此。这项工作对于理解临床耳鸣和听觉亢进至关重要，特别是将其与这些日益普遍的疾病的潜在神经机制的动物数据联系起来。

DESCRIPTION (provided by applicant): This proposal to examine classic indicators of sensorimotor gating - the acoustic startle response (ASR) and prepulse inhibition (PPI) - in humans with tinnitus and hyperacusis is both important and timely. It is motivated by (i) the almost complete absence of data on either ASR or PPI in relation to human tinnitus or hyperacusis, despite the success of these measures in objectifying and elucidating a variety of other conditions also thought to involve failures of inhibition and over-excitation, including schizophrenia, obsessive compulsive disorder and Tourette's syndrome, (ii) suggestions that enhanced ASR in animal models indicates hyperacusis, but a lack of data testing this hypothesis and, (iii) the recent surge of interest in a gap-detection startle reflex (GDSR) test fo tinnitus in animals, which has yet to be validated in humans and is reliant on the ASR and neural circuitry mediating PPI. The proposed experiments measuring ASR, PPI and GDSR in human subjects will test (1) whether insights into the mechanisms of tinnitus and hyperacusis might be leveraged from other more heavily studied neurological conditions for which the ASR and PPI are already well-characterized, and (2) whether ASR and GDSR measures thought to indicate hyperacusis and tinnitus in animals actually do. The proposed work is crucial to understanding clinical tinnitus and hyperacusis and, specifically, relating it to animal data on th underlying neural mechanisms of these increasingly prevalent disorders.